Absolute Levels and Ratios of Proinflammatory and Anti‐inflammatory Cytokine Production In Vitro Predict Clinical Immunity to<i>Plasmodium falciparum</i>Malaria

TLDR

Absolute levels and ratios of pro‑inflammatory and anti‑inflammatory cytokines influence susceptibility to infection, clinical disease, and anemia. The study examined how cytokine production in whole‑blood cultures relates to malaria outcomes and immunity in southern Ghana. Higher production of IFN‑γ, TNF‑α, IL‑12, and TGF‑β, and lower pro‑to‑anti‑inflammatory ratios, were linked to reduced fever, malaria, and parasitemia, while elevated ratios predicted higher fever and hemoglobin, contradicting cross‑sectional data and underscoring the need for detailed cellular immunity analyses.

Abstract

The relationship between malaria-related outcomes and cytokine production in whole blood cultures associated with cellular immune responses and immunity to Plasmodium falciparum malaria was examined in a study in southern Ghana. Production of malaria-specific interferon (IFN)-γ was associated with reduced risk of fever and clinical malaria. Protective IFN-γ responses were induced by live schizonts but not by dead parasites. Production of malaria-specific tumor necrosis factor (TNF)-α was associated with reduced risk of fever during follow-up. Baseline levels of TNF-α and phytohemagglutinin (PHA)-induced interleukin (IL)-10 were positively associated with hemoglobin concentration. IL-12 production was associated with reduced risk of parasitemia. PHA-induced transforming growth factor-β production was associated with reduced risk of fever during follow-up. High ratios of proinflammatory to anti-inflammatory cytokines were associated with increased risk of fever and higher hemoglobin concentrations. Thus, absolute levels and ratios of proinflammatory and anti-inflammatory cytokines influence susceptibility to infection, clinical disease, and anemia. These data contradict data from cross-sectional clinical studies and indicate a need for detailed analysis of the relationship between cellular immunity to malaria and resistance to disease.